The acute respiratory distress syndrome (ARDS) is a diffuse inflammatory lung disease that has been associated with both direct and indirect pulmonary insults. In ARDS, these diverse etiologies share a common histologic pattern known as diffuse alveolar damage in which the alveolar cells are damaged and the alveoli themselves become filled with proteinaceous fluid. As a result, oxygenation is severely impaired. Despite advances in clinical care mortality remains high and the development of ARDS pharmacotherapy remains a major unmet medical need. Historically, research has focused on the inflammatory processes that underlie ARDS. This led to several clinical trials of anti-inflammatory medications such as corticosteroids and non-steroidal anti-inflammatory drugs. This strategy sought to limit tissue damage but did not promote restoration of normal lung architecture per-se. To date, no anti-inflammatory medication has shown a convincing mortality benefit in ARDS. In this proposal we postulate that one reason anti-inflammatory medications have not shown a major benefit may be because the inflammatory cells themselves promote the restoration of normal lung architecture following ARDS. This project will enhance our insight into reparative mechanisms and bolster a therapeutic strategy that seeks to directly promote restoration of the alveolar epithelium as a treatment for ARDS. The scientific objective of this proposal is to determine how granulocyte-colony stimulating factor (G-CSF), a key regulator of neutrophil homeostasis, contributes to alveolar regeneration in a murine model of acid-induced lung injury, which is similar to human ARDS. Preliminary data suggests that these mice recruit fewer neutrophils to the alveoli following lung injury and also demonstrate significantly impaired alveolar repair three days after acid aspiration. The aims of this proposal are thus 1) elucidate i G-CSF promotes alveolar repair through a neutrophil dependent pathway and 2) investigate how G-CSF influences the proliferation and differentiation of alveolar type II pneumocytes, a key reservoir of progenitor type I pneumocytes, following lung injury. This proposal's other key objective is to train the candidate in the nascent field of pulmonary epithelial regeneration. This proposal outlines an individualized plan of mentoring, didactic coursework and professional development to help the candidate become a leader in understanding how innate inflammatory responses influence the repair mechanisms in the lung following ARDS.